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The Effect of ß-Adrenergic and Peroxisome Proliferator–Activated Receptor- Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue

¹ Molecular Endocrinology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
² Department of Animal Physiology, Faculty of Biology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
³ Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
⁴ Clinical Physiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana

Address correspondence and reprint requests to Steven R. Smith, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail: smithsr{at}pbrc.edu

OBJECTIVE—The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects.

RESEARCH DESIGN AND METHODS—A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression.

RESULTS—Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by –7.7, –24, –15.2, and –41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP.

CONCLUSIONS—Combined activation of peroxisome proliferator–activated receptor- and ß-adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism.

Abbreviations: CPT-1, carnitine palmitoyltransferase-1 • CT, computed tomography • EC, ephedrine HC1 plus caffeine • FATP/CD36, fatty acid transporter • LPL, lipoprotein lipase • MCAD; medium-chain acyl CoAdehydrogenase • MLYCD, malonyl-CoA decarboxylase • PGC-1, peroxisome proliferator–activated coactivator 1 • PPAR, peroxisome proliferator–activated receptor • SAT, subcutaneous adipose tissue • SCD-1, stearoyl-CoA desaturase-1 • UCP-1, uncoupling protein-1 • VAT; visceral adipose tissue • WAT, white adipose tissue

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